Advertisement

Research Article Free access | 10.1172/JCI115622

An osteopenic nonfracture syndrome with features of mild osteogenesis imperfecta associated with the substitution of a cysteine for glycine at triple helix position 43 in the pro alpha 1(I) chain of type I collagen.

J R Shapiro, M L Stover, V E Burn, M B McKinstry, A L Burshell, S D Chipman, and D W Rowe

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by Shapiro, J. in: JCI | PubMed | Google Scholar

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by Stover, M. in: JCI | PubMed | Google Scholar

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by Burn, V. in: JCI | PubMed | Google Scholar

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by McKinstry, M. in: JCI | PubMed | Google Scholar

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by Burshell, A. in: JCI | PubMed | Google Scholar

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by Chipman, S. in: JCI | PubMed | Google Scholar

Bone Metabolism Research Laboratory, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.

Find articles by Rowe, D. in: JCI | PubMed | Google Scholar

Published February 1, 1992 - More info

Published in Volume 89, Issue 2 on February 1, 1992
J Clin Invest. 1992;89(2):567–573. https://doi.org/10.1172/JCI115622.
© 1992 The American Society for Clinical Investigation
Published February 1, 1992 - Version history
View PDF
Abstract

Mutations affecting the pro alpha 1(I) or pro alpha 2(I) collagen genes have been identified in each of the major clinical types of osteogenesis imperfecta. This study reports the presence of a heritable connective tissue disorder in a family with an osteopenic syndrome which has features of mild osteogenesis imperfecta but was considered idiopathic osteoporosis in the proband. At age 38, while still premenopausal, she was found to have osteopenia, short stature, hypermobile joints, mild hyperelastic skin, mild scoliosis, and blue sclerae. There was no history of vertebral or appendicular fracture. Hip and vertebral bone mineral density measurements were consistent with marked fracture risk. Delayed reduction SDS-PAGE of pepsin-digested collagens from dermal fibroblast cultures demonstrated an anomalous band migrating between alpha 1(I) and alpha 1(III). This band merged with the normal alpha-chains upon prereduction, indicating an unexpected cysteine residue. Cyanogen bromide peptide mapping suggested that the mutation was in the smaller NH2-terminal peptides. cDNA was reverse transcribed from mRNA and amplified by the polymerase chain reaction. A basepair mismatch between proband and control alpha 1(I) cDNA hybrids was detected by chemical cleavage with hydroxylamine:piperidine. The cysteine substitution was thus localized to alpha 1(I) exon 9 within the cyanogen bromide 4 peptide. Nucleotide sequence analysis localized a G----T point mutation in the first position of helical codon 43, replacing the expected glycine (GGT) residue with a cysteine (TGT). The prevalence of similar NH2-terminal mutations in subjects with this phenotype which clinically overlaps idiopathic osteoporosis remains to be determined.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (February 1, 1992): No description
Advertisement
Advertisement